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Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

¹ Department of Diagnostic Radiology, ² The Laboratory of Biomedical Imaging and Signal Processing, Department of Electrical and Electronic Engineering, The University of Hong Kong, and ³ Department of Oncology, Princess Margaret Hospital, Hong Kong

Requests for reprints: Pek-Lan Khong, Department of Diagnostic Radiology, The University of Hong Kong, Blk. K, Room 406, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Phone: 852-28553307; Fax: 852-28551652; E-mail: plkhong{at}hkucc.hku.hk.

Key Words: diffusion tensor imaging • white matter • rat • radiation

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (_//), and radial diffusivity () can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in _// from 4 to 40 weeks postradiation, and an increase in with return to baseline in _// at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in _// correlated with reactive astrogliosis (P < 0.01) and correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in _// and . DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage. [Cancer Res 2009;69(3):1190–8]